Borane;tetrahydrofuran → HCID 24889561, compound

HRID 1410370Notes

Reaction equation

HRID 1410370 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:21]=[C:22]4[N:26]([CH:27]=3)[C:25]3[CH:28]=[CH:29][C:30]([CH2:32][CH2:33][C:34](=O)[N:35]5[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]5)=[CH:31][C:24]=3[S:23]4)=[CH:16][CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].B.C1COCC1>C1COCC1>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[N:21]=[C:22]4[N:26]([CH:27]=3)[C:25]3[CH:28]=[CH:29][C:30]([CH2:32][CH2:33][CH2:34][N:35]5[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]5)=[CH:31][C:24]=3[S:23]4)=[CH:18][CH:19]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuran2×HCID 66592956HCID 66592956, compound

Product 1

HCID 24889561HCID 24889561, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(3-oxo-3-piperidin-1-yl-propyl)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea from Example 12C (0.36 g, 0.63 mmol) in THF (10 mL) at room temperature was added 1.0 M solution of BH3/THF in THF (10 mL). The mixture was heated to reflux over night, but LC-MS showed the reaction was not complete. Therefore, additional 5.0 mL of 1.0 M BH3/THF solution was added and heated to reflux for 8 hours. The reaction was quenched by dropwise addition of 10% HCl solution and stirred at room temperature for 20 min. The mixture was basified with saturated NaHCO3 solution and extracted with dichloromethane. The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by Flash chromatography with silica gel using a 0-10% methanol/dichloromethane gradient. The appropriate fractions were collected, combined, and concentrated to give free base, N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(3-piperidin-1-yl-propyl)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea (0.182 g). 1H NMR (DMSO-d6) δ 9.54 (s, 1H), 8.88 (s, 1H), 8.67 (s, 1H), 7.90 (s, 1H), 7.88 (d, 1H), 7.79 (d, 2H), 7.53 (d, 2H), 7.45 (d, 1H), 6.53 (s, 1H), 2.75 (m, 8H), 2.05 (m, 2H), 1.67 (m, 2H), 1.47 (m, 4H), 1.30 (s, 9H); 13C NMR (DMSO-d6) δ 180.55, 158.75, 151.65, 146.97, 146.42, 138.99, 138.38, 130.52, 129.59, 128.77, 127.27, 125.58, 124.70, 119.05, 113.37, 108.58, 92.81, 65.28, 57.96, 32.90, 28.72, 24.93, 22.55, 20.24, 15.53; LC-MS: ESI 557 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux over night
  3. temperatureheated
  4. temperatureto reflux for 8 hours
  5. customThe reaction was quenched by dropwise addition of 10% HCl solution
  6. extractionextracted with dichloromethane
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by Flash chromatography with silica gel using a 0-10% methanol/dichloromethane gradient
  10. customThe appropriate fractions were collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-ea445225414b4b578e600d820618884b
Source dataset
uspto-grants-2014_12
Patent number
US08921546B2

Reaction notes

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